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MDC Researchers Identify a Scaffold Regulating Protein Disposal

How does a cell manage to identify and degrade the diverse types of defective proteins and thus protect the body against serious diseases? The researchers Sabine C. Horn, Professor Thomas Sommer, Professor Udo Heinemann and Dr. Ernst Jarosch of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now found a crucial piece in this puzzle. In an enzyme complex that plays a critical role in the quality control of proteins, they discovered a scaffold regulating the identification and disposal of various defectively produced proteins. (Molecular Cell, doi: 10.1016/j.molcel200910.015)*.

Harvard Immunologist Klaus Rajewsky Receives Max Delbrück Medal

The German immunologist Professor Klaus Rajewsky from Harvard Medical School in Boston, USA, has received the Max Delbrück Medal in Berlin, Germany. The jury from various Berlin-based research institutions* honored him for his work on the development and function of B cells, the antibody factories of the body. He developed a technique to delete genes in mice in specific tissue and under specific conditions, which enabled him to explore the role of B cells within the immune system. This technique has become one of the most important tools to study human diseases in mice and is used today in research laboratories all over the world. Professor Rajewsky was also honored for his research on the development of lymphomas, especially Hodgkin’s lymphoma.

There are approximately 400 different skeletal muscle diseases, each of which is rare and incurable. Furthermore, there is no structured platform for PhD training in this field. This shall soon change. The German Research Foundation (DFG) and the Université Pierre et Marie Curie Paris VI (UPMC), Paris, France are now establishing the first international, structured PhD program in myology at the Experimental and Clinical Research Center (ECRC) in Berlin-Buch and at the UPMC in Paris. “The International Research Training Group for Myology” (MyoGrad) shall begin on April 1, 2010 for a funding period of four and one-half years.

MDC Scientists Show How Hematopoietic Stem Cell Development Is Regulated

During cell division, whether hematopoietic stem cells (HSCs) will develop into new stem cells (self-renewal) or differentiate into other blood cells depends on a chemical process called DNA methylation. These were the findings of researchers at the laboratory of Dr. Frank Rosenbauer of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch in cooperation with the laboratory of Professor Sten Eirik W. Jacobsen (Lund University, Sweden and the University of Oxford, England). Furthermore, the researchers showed that DNA methylation also plays a crucial role for cancer stem cells (Nature Genetics, online, doi: doi:10.1038/ng.463)*.

Professor Jens Reich of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch has been honored with the Carl Friedrich von Weizsäcker Award of the National Academy of Sciences Leopoldina and the Stifterverband für die Deutsche Wissenschaft. The physician, bioinformatician, molecular biologist and GDR civil rights activist received the award for his exceptional scientific achievements and his personal and political courage. The award was presented to him at the annual assembly of Leopoldina on October 2nd in Halle (Saale), Germany. He is the first recipient of the 50,000 Euro award.

MDC Researchers Discover Molecule Responsible for Axonal Branching

The human brain consists of about 100 billion (1011) neurons, which altogether form about 100 trillion (1014) synaptic connections with each other. A crucial mechanism for the generation of this complex wiring pattern is the formation of neuronal branches. The neurobiologists Dr. Hannes Schmidt and Professor Fritz G. Rathjen at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now discovered a molecule that regulates this vital process. At the same time they have succeeded in elucidating the signaling cascade induced by this molecule (PNAS, Early Edition, 2009, doi:10.1073)*.

A European Research Council (ERC) Starting Grant worth more than a million euros over the next five years has been awarded to Dr. Francesca M. Spagnoli of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany. For nearly a year Dr. Spagnoli has been leading a Helmholtz junior research group at MDC, an institution of the Helmholtz Association, and at Charité – Universitätsmedizin Berlin. Together with the biophysicist Dr. Leif Schröder from the Leibniz Institut für Molekulare Pharmakologie (FMP), also on the Berlin-Buch Campus, Dr. Spagnoli belongs to the 240 top scientists the ERC has chosen from more than 2, 500 applicants.

Aarhus University in Denmark has awarded an honorary doctorate to the cell biologist Professor Thomas Willnow of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. The university honored him for his achievements in biomedical research and their implementation into practice (translational research) at Aarhus University. The title “Doctor Medicinae Honoris Causa” (dr.med.h.c.) was conferred at a ceremony on September 11, 2009 in connection with the university’s 81st anniversary.

A Rapid and Efficient Cell Sorting Method Allows New Insights into Early Animal Embryogenesis - Close Collaboration between Max Delbrück Center and New York University

Caenorhabditis elegans (C. elegans) is one of the most important model systems in biology. A technique to collect large numbers of embryos of the animals, all precisely the same age, has been developed in a collaborative effort by researchers from the Max Delbrück Center (MDC) in Berlin, Germany and New York University (NYU), USA. This new technique (termed eFACS) and subsequent molecular analysis of small RNAs are reported online this week in Nature Methods (DOI 10.1038/nmeth.1370). eFACS opens the door for detailed and quantitative high-throughput studies of early events during embryogenesis of C. elegans, a prerequisite for Systems Biology approaches. Using eFACS, the researchers were already able to reveal that small RNA expression during early embryogenesis is a highly orchestrated and complex process.

MRI Specialist Thoralf Niendorf Appointed Professor in Berlin-Buch

The physicist Professor Thoralf Niendorf has been appointed to the chair of Experimental Ultra High Field Magnetic Resonance Imaging (MRI) at the Experimental and Clinical Research Center (ECRC) of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité – Universitätsmedizin Berlin, Germany. Since August 10, 2009 the specialist for imaging techniques from RWTH Aachen University heads the MRI facility of the ECRC on Campus Berlin-Buch. The research facility with one of the world’s strongest magnetic resonance tomographs, a 7 Tesla whole-body MRI scanner, was dedicated in January 2009 by Professor Annette Schavan, Germany’s Federal Minister of Education and Research.

Estrogen-Dependent Switch Tempers Killing Activity of Immune Cells

The sex hormone estrogen tempers the killing activity of a specific group of immune cells, the cytotoxic T cells (CTLs), which are known to attack tumor cells and cells infected by viruses. The key player in this process is a cytotoxic T cell molecule which has been known for a long time and which scientists have named EBAG9. Cancer researchers Dr. Constantin Rüder and Dr. Armin Rehm together with immunologist Dr. Uta Höpken of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité – University Medicine Berlin, Germany, have now unraveled the function of EBAG9. Modulated by estrogen, EBAG9 tempers the activity of CTLs. In the absence of EBAG9, the activity of CTLs is enhanced (Journal of Clinical Investigation, Vol. 119, No. 8, pp 2184-2203, August 3, 2009)*.

International Research Team seeks to Unravel Flatworm Regeneration

Planarian flatworms are only a few millimeters up to a few centimeters in length, live in freshwater and are the object of intense research, because they possess the extraordinary ability to regenerate lost tissue with the help of their stem cells (neoblasts) and even grow an entirely new worm out of minute amputated body parts. Now researchers from the Max Delbrück Center in Berlin, Germany together with researchers in the US and Canada present the first comprehensive catalogue of small RNAs of planaria, elements that regulate gene expression. They also have identified small RNAs which may play a role in regeneration and stem cell function, Nikolaus Rajewsky from the MDC points out (PNAS, Early Edition)*.

Gliomas exploit Immune Cells of the Brain for Rapid Expansion

Gliomas are among the most common and most malignant brain tumors. These tumors infiltrate normal brain tissue and grow very rapidly. As a result, surgery can never completely remove the tumor. Now, the neurosurgeons Dr. Darko S. Markovic (Helios Klinikum Berlin-Buch) and Dr. Michael Synowitz (Charité) as well as Dr. Rainer Glass and Professor Helmut Kettenmann (both Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch), have been able to show that glioma cells exploit microglia, the immune cells of the brain, for their expansion (PNAS Early Edition)*.

Previously, only a few genes had been associated with the formation of metastases in colorectal cancer. Now, researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité – University Medicine Berlin, Germany, have identified 115 genes that are disregulated both in the primary tumor and in its metastases. In the future, their findings may help identify patients with aggressive tumors at an earlier stage (Gastroenterology 2009, doi:10.1053/j.gastro.2009.03.041).*

New Control System of the Body Discovered – Important Modulator of Immune Cell Entry into the Brain – Perhaps New Target for the Therapy

Researchers in Berlin, Germany have ameliorated inflammation of the brain in mice caused by immune cells. A receptor they discovered on the surface of T cells in the central nervous system (CNS) plays the key role. The researchers showed that this bradykinin receptor 1 (B1) controls the infiltration of immune cells into the CNS. When they activated B1 in mice with encephalitis, they were able to slow down the crossing of the immune cells through the blood-brain-barrier into the CNS. As a result, the inflammation markedly decreased. The work by Dr. Ulf Schulze-Topphoff, Prof. Orhan Aktas, and Professor Frauke Zipp (Cecilie Vogt-Clinic, Charité – Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and NeuroCure Research Center) together with researchers in Canada and the USA may unveil a new target for the treatment of chronic inflammatory diseases such as multiple sclerosis (MS) (Nature Medicine, doi 10.1038/nm.1980)*.

A lack of serotonin, commonly known as the “happiness hormone”, in the brain slows the growth of mice after birth and is responsible for impaired maternal behavior later in life. This was the result of research conducted by Dr. Natalia Alenina, Dana Kikic, and Professor Michael Bader of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany. At the same time, the researchers discovered that the presence of serotonin in the brain is not crucial for the survival of the animals. Furthermore, they were able to confirm that there are two strictly separate pathways of serotonin production: One gene is responsible for the formation of serotonin in the brain, another gene for the production of the hormone in the body (PNAS, June 23, 2009, Vol. 106, No. 25, pp 10332-10337)*.

Immune cells Ameliorate Hypertension-Induced Cardiac Damage in Mice

Researchers in Berlin, Germany have found that a specific type
of immune cell, the regulatory T lymphocyte (Treg) plays an important role in
hypertension-induced cardiac damage. The injected Treg that they harvested from
donor mice into recipient mice were infused with angiotensin II, a blood
pressure-raising peptide. The Tregs had no influence on the blood pressure
response to angiotensin II. Nonetheless, cardiac enlargement, fibrosis, and
inflammation was sharply reduced by Treg treatment. Furthermore, the tendency
to develop abnormal heart rhythms that could lead to sudden cardiac death was
also reduced. Dr. Heda Kvakan
and Dr. Dominik N. Müller at the Experimental and ClinicalResearchCenter
at the MaxDelbrückCenter
do not intend Treg as a therapy. However, a better understanding of how
the immune system fits into hypertension-induced organ damage could result from
these studies (Circulation, Vol. 119,
No. 22, June 9, 2009, 2904-2912 ).*

Investigating the Development of Mechanosensitivity

Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have gained crucial insight into how mechanosensitivity arises. By measuring electrical impulses in the sensory neurons of mice, the neurobiologists and pain researchers Dr. Stefan G. Lechner and Professor Gary Lewin were able to directly elucidate, for the first time, the emergence of mechanosensitivity. At the same time they were able to show that neurons develop their sensitivity to touch and pain during different developmental phases but always coincidentally with the growth of the neuronal pathways. (EMBO Journal, 2009, doi:10.1038/emboj.2009.73).*

3D Kidney Atlas Created for Researchers and Physicians

Renal diseases shall be diagnosed earlier and treated more successfully in the future. Towards this aim, researchers from nine European countries*, coordinated by the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have been working for the past four-and-a half years to create a three-dimensional virtual “Kidney Atlas”. It incorporates the latest research findings on the development and diseases of the kidney. The Kidney Atlas was part of the European Renal Genome Project (EuReGene), which the European Union (EU) funded with more than 10 million euros. At the conclusion of the project, the Kidney Atlas was presented at MDC during a two-day symposium from May 15-16, 2009, which was attended by approximately 100 researchers.

MDC Researchers Unravel Key Mechanism in Pathogenesis of Osteoporosis

Osteoporosis, or bone loss, is a disease that is most common in the elderly population, affecting women more often than men. Until now, it was not clear exactly how the disease develops. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now elucidated a molecular mechanism which regulates the equilibrium between bone formation and bone resorption. Dr. Jeske J. Smink, Dr. Valérie Bégay, and Professor Achim Leutz were able to show that two different forms of a gene switch – a short isoform and a long isoform – determine this process. The MDC researchers hope these findings will lead to new therapies for this bone disease. (EMBO Journal)*.

New Light Shed on the Enigma of Salt Intake and Hypertension

A high salt intake has been implicated in cardiovascular disease risk for 5000 years. But salt-sensitive hypertension still remains an enigma. Now, investigators from Germany at the University of Erlangen, the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Regensburg, collaborating with researchers from Finland and Austria have shed new light on the relationship between salt intake, bodily processes, and blood pressure regulation. Within the skin, they have detected a new storage area for salt in the body. They also found out that if the process behind this storage is defect, animals become hypertensive (Nature Medicine, doi 10.1038/nm.1960)*.

Scientists from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany have succeeded in generating a hyperactive “jumping gene” (a transposon) and hope to have an improved tool for basic research and gene therapy. “The new transposon system is able to introduce genes into cells and to stably insert them into the cell’s genome at an unprecedented efficiency,” Dr. Lajos Mátés, Dr. Zoltán Ivics and Dr. Zsuzsanna Izsvák point out. They worked together with scientists from the Catholic University of Leuven, Belgium (Nature Genetics, doi: 10.1038/ng.343).*

Gene Test Determines Risk of Heart Surgery Complications

Genetic differences can explain why some patients undergoing heart surgery later experience shock and kidney complications, according to a study by researchers at the Charité – Universitätsmedizin Berlin, the Max-Delbrück-Center for Molecular Medicine (MDC) Berlin-Buch in Germany and the Austin Hospital in Melbourne, Australia. The results indicate that performing a genetic test on patients before they have surgery can help guide treatment after they leave the operating room (Journal of the American Society of Nephrology, JASN, doi 10.1681/ASN.2008080915)*.

MPI and MDC Researchers Make Significant Strides in Identifying Cause of Bacterial Infections

Several
bacterial pathogens use toxins to manipulate human host cells, ultimately disturbing
cellular signal transduction. Until now, however, scientists have been able to track
down only a few of the proteins that interact with bacterial toxins in infected
human cells. Now, researchers of the Max Planck Institute of Biochemistry in
Martinsried and the Max Delbrück Center for Molecular Medicine (MDC)
Berlin-Buch in Germany have identified 39 interaction partners of these toxins,
using novel technology which allowed them to screen for large numbers of
proteins simultaneously (Cell Host & Microbe,
Vol. 5, Issue 4, 397-403)*.

New Risk Variant for Atopic Dermatitis Identified

Scientists of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité – University Medical School, Berlin, Germany, in collaboration with researchers from the Klinikum rechts der Isar of Technical University Munich and Christian Albrecht University, Kiel, have identified a gene variant on chromosome 11 that is associated with an increased risk of atopic dermatitis. In a large genome-wide association study the researchers scanned the genomes of more than 9600 participants from Germany, Poland and the Czech Republic. “Our findings cast new light on the pathogenesis of the disease,” said Professor Young-Ae Lee (Charité / MDC). The pediatrician-researcher and her collaborators hope the study will lead to a new approach to targeted therapy for this chronic skin disorder. (Nature Genetics doi: 10.1038/ng.347)*.

Life-threatening cardiac arrhythmia can be a consequence of myocarditis – an inflammation of the cardiac muscle that can be caused by the Coxsackievirus. In mice, Dr. Yu Shi, Chen Chen, and Professor Michael Gotthardt of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now abolished the infection by blocking the receptor which is required for virus entry. “We did not detect a single cardiomyocyte that was infected by the virus. Inflammation of the heart muscle associated with this virus infection did not develop,” Dr. Shi said. (Journal of the American College of Cardiology, 2009; 53:1219-1226, doi:10.1016/j.jacc.2008.10.064).*

What Sets the Stone Rolling - New Insights into Cancer Pathogenesis

Dr. Stephan Mathas and Professor Bernd Dörken of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité – Medical University Berlin, in close cooperation with Professor Tom Misteli of the National Cancer Institute, Bethesda, MD, USA, have identified three cancer genes involved in the pathogenesis of a cancer of the lymphatic system. At the same time they were able to shed light on the translocation process, which also plays a crucial role in cancer pathogenesis. During translocation, fragments of genes move from one chromosome to another and fuse – if they are close enough to each other – to a new gene. This fusion gene additionally stimulates the growth of cancer genes. (PNAS, Early Edition, 2009, doi:10.1073/pnas.0900912106).

Professor Jens Reich Turns 70

Professor emeritus Jens Reich, physician, molecular biologist and civil rights activist, celebrates his 70th birthday on March 26, 2009. Since retiring five years ago from the Max Delbrück Center for Molecular Medicine, he has remained active in research. Through genome database searches and analysis he seeks to identify genes that are important for cholesterol metabolism. Currently he is coordinating a research network project at MDC together with a research group at the European Molecular Biology Laboratory (EMBL), Heidelberg and the University of Heidelberg on the systems biology of human iron metabolism and its pathological dysregulation.

New Insights into Cell Migration and Tissue Morphogenesis in Zebrafish

Using
zebrafish embryos as a model system, researchers of the Max Delbrück Center for
Molecular Medicine (MDC) Berlin-Buch have gained new insights into the complex
morphogenesis of epithelial cells during their development and migration. David
Hava, Dr. Ulrike Forster and Dr. Salim Abdelilah-Seyfried studied the
development of the lateral line organ in zebrafish, a sensory system found in
fish and amphibians which serves to detect water flow and movements. Their
findings show that two genes regulate cell organization within this epithelial
tissue, which is found at different points along the fish body surface. Both
genes also play a role in cancer development. (Journal of Cell Science, 10.
February 10, 2009, doi: 10.1242/jcs.032102)*.

Physician Professor Walter Rosenthal has been
appointed as Scientific Director of the Max Delbrück Center for Molecular
Medicine (MDC) Berlin-Buch, an institute which belongs to the Helmholtz
Association of National Research Centers. Professor Rosenthal, the former
director of the Leibniz-Institut für Molekulare Pharmakologie (FMP) succeeds
cancer researcher Professor Walter Birchmeier who has served as the MDC Scientific Director for the past five years and who will now return his focus to his MDC
research group. Professor Hartmut Oschkinat shall hold the office of Acting
Director of the FMP until a successor has been appointed. Both institutes are
located on the Berlin-Buch Campus and have been working together for many
years.